Patients with
Cushing syndrome have elevated 24 h urinary free
cortisol excretion and loss of diurnal rhythm of plasma
cortisol, however, morning total plasma
cortisol concentrations are often similar to those of normal individuals. To test the hypothesis that an elevated morning plasma free
cortisol could distinguish patients with
Cushing syndrome from those without the disorder, we measured plasma free
cortisol levels at 08:00 in 20 patients with surgically-confirmed mild
Cushing syndrome, 19 patients with pseudo-Cushing states, and 9 normal volunteers. We then determined the sensitivity, specificity and diagnostic accuracy of plasma free
cortisol for the diagnosis of
hypercortisolism and for the diagnosis of
Cushing syndrome. Plasma free
cortisol was compared to 08:00 total plasma
cortisol and to basal 24 hour urinary free
cortisol. Morning plasma free
cortisol was significantly elevated in patients with mild
Cushing syndrome (58 +/- 6 nmol/L; mean +/- SE) compared to plasma free
cortisol in patients with pseudo-Cushing states (36 +/- 6 nmol/L) (p < 0.005) and normal volunteers (22 +/- 4 nmol/L) (p < 0.0005). Total morning
cortisol was significantly greater in patients with mild
Cushing syndrome (470 +/- 28 nmol/L) than in normal volunteers (310 +/- 33 nmol/L, p < 0.05) but was not different from patients with pseudo-Cushing states (410 +/- 47 nmol/L, p = NS). Urinary free
cortisol was also significantly greater in mild
Cushing syndrome (540 +/- 50 nmol/d) than in patients with pseudo-Cushing states (430 +/- 41 nmol/d, p < 0.05) or normal volunteers (160 +/- 28 nmol/d, p < 0.0001). However, there was considerable overlap of plasma free
cortisol, plasma total
cortisol and urinary free
cortisol between the three groups precluding these tests alone from being useful to distinguish patients with mild
Cushing syndrome from patients with pseudo-Cushing states. To achieve 100% sensitivity for the diagnosis of
Cushing syndrome, the specificity for plasma free
cortisol, plasma total
cortisol and urinary free
cortisol was 0.11, 0.32 and 0.32, respectively. We conclude that plasma free
cortisol is of limited value in the differential diagnosis of
hypercortisolism.